ABSTRACT
BACKGROUND: Patients with late-onset Pompe disease develop progressive hypercapnic respiratory failure that can be disproportionate to the respiratory muscle compromise and/or thoracic restriction. Although recent studies have reported the presence of a blunted hypercapnic respiratory response in some subjects with neuromuscular disorders and chronic hypercapnia, no study has evaluated the integrity of the respiratory drive in subjects with late-onset Pompe disease. Thus, we endeavor to determine the CO2 rebreathing response in subjects with late-onset Pompe disease. METHODS: Respiratory muscle strength was assessed by measuring the maximum inspiratory pressure, and the maximum expiratory pressure. The maximum inspiratory pressure reflects the strength of the diaphragm and other inspiratory muscles, whereas the maximum expiratory pressure reflects the strength of the abdominal muscles and other expiratory muscles. We studied the hypercapnic drive response (measured as the ratio of the change in airway-occlusion pressure 0.1 s after the start of inspiration and end-tidal PCO2 in 13 subjects with late-onset Pompe disease and 51 healthy controls. RESULTS: Overall inspiratory muscle strength was within normal limits or slightly diminished in the late-onset Pompe disease group. Five subjects (38.5%) were chronically hypercapnic, and 9 (69.2%) had an increased breath-holding time. Compared with controls, the change in airway-occlusion pressure 0.1 s/change in end-tidal CO2 pressure slope (hypercapnic respiratory drive) was lower in the late-onset Pompe disease group (median 0.050 [interquartile range 0.027-0.118] vs 0.183 [0.153-0.233], P < .001). Nine subjects (69.2%) had a blunted change in airway-occlusion pressure 0.1 s/change in end-tidal carbon dioxide pressure slope. CONCLUSIONS: Subjects with late-onset Pompe disease had an impaired hypercapnic respiratory drive response. The clinical impact of this phenomenon in this subject subset deserves further investigation.
Subject(s)
Glycogen Storage Disease Type II/physiopathology , Hypercapnia/physiopathology , Late Onset Disorders/physiopathology , Respiratory Insufficiency/physiopathology , Respiratory Mechanics/physiology , Adolescent , Adult , Carbon Dioxide/physiology , Case-Control Studies , Female , Glycogen Storage Disease Type II/complications , Humans , Hypercapnia/etiology , Late Onset Disorders/complications , Male , Maximal Respiratory Pressures , Middle Aged , Muscle Strength , Respiratory Insufficiency/etiology , Respiratory Muscles/physiopathology , Young AdultABSTRACT
La ventilación pulmonar en humanos tiene una variabilidad respiración a respiración no lineal, compleja y caótica. El objetivo del trabajo fue: caracterizar la variabilidad del patrón respiratorio en perros (n: 8) anestesiados respirando bajo carga elástica umbral (CEU) inspiratoria (7 a 50 cm H2O). Con el flujo, presión traqueal y esofágica, se analizaron: tiempo inspiratorio (Ti), ritmo [tiempo espiratorio (Te); tiempo total (Ttot), y Ti/Ttot] e impulso central (Vt/Ti), variables relacionadas [volumen corriente (Vt) y ventilación pulmonar (Ve)]. Se determinaron: variabilidad grosera (varianzas), oscilaciones de baja frecuencia (análisis espectral) y memoria a corto plazo (análisis de autocorrelación). La CEU produjo disminución de la varianza de medias en Te, Ttot, Vt y Vt/Ti (p < 0.05). La media de las varianzas del Ti/Ttot aumentó (p < 0.005) y disminuyó para el Vt y el Vt/Ti (p < 0.05). En general, el porcentaje de oscilaciones de baja frecuencia (OB%) disminuyó (p < 0.02). Durante CEU alta, las variables de ritmo no cambiaron el porcentaje de registros con autocorrelación (AU%), pero el Vt y variables relacionadas disminuyeron los AU% (p < 0.005). Hubo correlación positiva (r: 0.955, p< 0.001) entre OB% y AU% en Vt y variables relacionadas, pero las variables de ritmo no mostraron correlación. En conclusión: La CEU indujo un patrón respiratorio más monótono. La memoria a corto plazo disminuyó en la fase inspiratoria y aumentó en la espiratoria. Estos cambios ocurrieron bajo anestesia, sugiriendo que ciertas estructuras suprapontinas pueden no ser imprescindibles para la generación de estos cambios.
In humans, lung ventilation exhibits breath-to-breath variability and dynamics that are nonlinear, complex and chaotic. Our objective was to characterize the breathing pattern variational activity in anesthetized dogs (n: 8) breathing through threshold inspiratory elastic load (7 to 50 cm H2O). Starting from flow signal and tracheal and esophageal pressures, we analyzed inspiratory time (Ti), timing (expiratory time, Te; total time, Ttot; and Ti/Ttot) and central drive (Vt/Ti) and variables related to it (tidal volume, Vt and pulmonary ventilation, Ve). We measured gross variability (variances), low frequency oscillations (spectral analysis), and short term memory (autocorrelation analysis). Loading decreased variance of the mean values of Te, Ttot, Vt and Vt/Ti (p < 0.05); the mean of variances for Ti/Ttot increased (p < 0.005) while it decreased for Vt and Vt/Ti (p < 0.05). In general, percent of data recordings with low frequency oscillations (OB%) decreased (p < 0.02). During heavy load, timing parameters percent of data recordings with autocorrelations (AU%) did not change, but Vt and its related parameters decreased their AU% (p < 0.005). There was a positive correlation (r: 0.955, p < 0.001) between the existence of low frequency oscillations and autocorrelations for Vt and its related parameters, while timing variables did not show such a correlation. In conclusion, threshold elastic load induced a monotonous respiratory pattern. The short term memory decreased during inspiratory stage while increased during expiratory stage. These changes occurred during anesthesia suggesting that certain suprapontine structures may not be obligatory to induce them.